Breast Cancer & the Environment:

Presented by: Ruthann Rudel, MS Director of Research Silent Spring Institute Megan Schwarzman, MD, MPH Research Scientist Center for Occupational and Environmental Health, University of California, Berkeley

The Growing Evidence

Agenda

What is being done to reduce exposures to toxic chemicals

Studying environmental links to breast cancer

Developing improved methods for identifying toxic chemicals

What you can do to help strengthen chemical safety in the US

Our Mission

Breast Cancer Action carries the

voices of people affected by breast cancer in order to inspire and

compel the changes necessary to end the breast cancer epidemic.

BCAction’s Strategic Priorities

(1) Putting Patients First

(2) Creating Healthy Environments

(3) Eliminating Social Inequities

Presenter slide

Ruthann Rudel, MS Silent Spring Institute

Presenter slide

Megan Schwarzman, MD, MPH Center for Occupational & Environmental Health, UCB

Environmental Chemicals and Breast Cancer

Opportunities for Prevention

Ruthann Rudel Breast Cancer Action webinar June 2014

w w w. s i l e n t s p r i n g . o r g

“… the true burden of environmentally induced cancer has been grossly underestimated”

w w w. s i l e n t s p r i n g . o r g

Breast cancer in a global context

1. Forouzanfar, M. Breast and cervical cancer in 187 countries between 1980 and 2010: a systemic analysis

• The most common cancer in women worldwide.

• Incidence is rising in

developing nations.1

• Risk changes when women migrate

w w w. s i l e n t s p r i n g . o r g

Breast cancer risk factors • Family history • Ionizing radiation • Reproductive history – menarche,

menopause, births • Overweight after menopause • Pharmaceutical hormones: HRT, DES • Alcohol • Lack of physical exercise • Tobacco smoke

Carcinogens / Hormones

w w w. s i l e n t s p r i n g . o r g

How might environmental

chemicals play a role?

w w w. s i l e n t s p r i n g . o r g

What kinds of studies reveal cancer causes?

• High, well-defined exposures among large groups

Not exposed

Exposed

Disease No disease

w w w. s i l e n t s p r i n g . o r g

What kinds of studies reveal cancer causes?

• Occupational studies – Men, chemicals, cancers (not breast)

• Accidents/disasters (e.g. ionizing radiation) • Pharmaceuticals (e.g. HRT)

www.silentspring.org

w w w. s i l e n t s p r i n g . o r g

60+ years to develop human evidence of DES-breast cancer link

“Every Group 1 agent can be considered to represent cancers that might have been prevented had scientists been able to predict cancer hazards earlier or had public health authorities been willing to act more quickly when scientific information became available.”

Cogliano et al. 2011 based on review of >100 IARC carcinogens in IARC Monograph vol. 100

Hoover et al, 2011

First lawsuit for breast cancer from DES settled in 2012

w w w. s i l e n t s p r i n g . o r g

Cancer Prevention Science

Biological mechanism

Human exposure

Basis for action

+

Educate Regulate

Reformulate

Biological mechanism

Human exposure

Educate Regulate

Reformulate

Strength of evidence, not “proof”

w w w. s i l e n t s p r i n g . o r g

Biological Mechanisms

• Mammary carcinogens damage DNA

• Endocrine disruptors as tumor promotors

• Endocrine disruptors as developmental toxicants that alter susceptibility

w w w. s i l e n t s p r i n g . o r g

Example Mammary Carcinogen Exposures

• Ionizing Radiation

• Gasoline

• Auto Exhaust, Air Pollution

• Paint Remover, Solvents

• Flame Retardants

• Pesticides

• Moldy Grain

• Water Disinfection Byproducts

• Nonstick Coatings

• Benzene

• PAHs

• Ethylene Oxide

• Methylene Chloride

Rudel et al., 2007, Cancer Rudel et al., 2014 EHP

w w w. s i l e n t s p r i n g . o r g

The breast is vulnerable during development

• Before birth • Puberty • Pregnancy

w w w. s i l e n t s p r i n g . o r g

We need chemicals testing to prevent breast cancer

Federal Interagency

Institute of Medicine President’s Cancer Panel Yet only 3% of National Institutes of Health $$ goes for

environmental health

w w w. s i l e n t s p r i n g . o r g

What does chemical safety testing have to do with breast

cancer?

We want . . . – chemicals evaluated for safety – tests relevant to breast

cancer

w w w. s i l e n t s p r i n g . o r g

Animal models and in vitro (cell-based)

• Identify potential carcinogens • Reveal mechanisms

• Used for drug discovery and chemical safety testing

w w w. s i l e n t s p r i n g . o r g

Animal studies

• 216 chemicals found to cause mammary tumors in rodents

• Animals typically exposed only as adults

www.silentspring.org Rudel et. al 2007 Cancer

w w w. s i l e n t s p r i n g . o r g

Animal studies • Rats aren’t people! • But rodent and human results are generally consistent

Exposure Human Breast

Cancer Rodent Mammary

Tumors HRT (E + P) + + HRT (E) (+) + Oral Contraceptives (E + P) + + DES + +

Griseofulvin, Furosamide, Metronidazole (+) + Indomethacin, Nitrofurantin (-) + Ionizing radiation + + Alcohol + (+) Heterocyclic amines (meat) (+) + Sleep disruption (+) + Ethylene oxide (+) + PAH (+) + Solvents (+) + DDE (tested in adult) - - DDT (early exposure) (+) Not tested

PCBs (testing adults, entire population) - - PCBs (polymorphism) (+) Not tested Dioxin (early exposure) (+) (+)

Rudel et. al 2014 Environmental Health Perspectives

Key

Pink & orange (+)

Positive association

Blue (-) Negative association

w w w. s i l e n t s p r i n g . o r g

Rudel et. al 2014 Environmental Health Perspectives

w w w. s i l e n t s p r i n g . o r g

Future: Faster, cheaper chemical safety tests

w w w. s i l e n t s p r i n g . o r g

Because chemical exposures are so

widespread, even a “small” influence on cancer risk touches

many lives

www.SilentSpring.org

Megan Schwarzman, MD, MPH

UC Berkeley School of Public Health

THE BREAST CANCER AND CHEMICALS POLICY PROJECT

What body of information –obtained using existing test methods– could best identify chemicals that may

increase the risk of breast cancer?

Core question

Project Goals

1. Design an approach for identifying chemicals that may contribute to the development or progression of breast cancer;

2. Identify research needs and recommend improvements to existing test methods; and

3. Pilot a model process that can be applied to other disease endpoints, as a step toward the ultimate aim of producing a comprehensive approach for identifying hazardous chemicals.

Expert panel • Susan Braun, MA - Commonweal

• Vincent James Cogliano, PhD - WHO International Agency for Research on Cancer

• Shanaz Dairkee *, PhD - California Pacific Medical Center Research Institute

• Suzanne Fenton, PhD - National Institute of Environmental Health Sciences

• William H. Goodson III, MD - California Pacific Medical Center Research Institute

• Joe Guth *, PhD, JD - Science and Environmental Health Network

• Dale Johnson, PharmD, PhD - University California Berkeley & Emiliem

• Jean Latimer, PhD - School of Medicine University of Pittsburgh

• Ron Melnick, PhD - National Institute of Environmental Health Sciences

• Rachel Morello-Frosch, PhD, MPH - University of California Berkeley

• Ruthann A. Rudel, MS - Silent Spring Institute

• Gina Solomon*, MD, MPH - UCSF & Natural Resources Defense Council

• Carlos Sonnenschein, MD -Tufts University School of Medicine

• Lauren Zeise*, PhD Cal/EPA Office of Environmental Health Hazard Assessment

* Indicates a member of the core panel, which met monthly throughout the project

Steps of the Breast Cancer and Chemicals Policy Project

STEP 1 Identify toxicity “endpoints”, alterations in

biological processes that

increase the risk of breast cancer

STEP 2 Identify toxicity testing methods

to detect chemicals that alter biological

processes relevant to

breast cancer

STEP 3 Propose an

approach for prioritizing and

testing chemicals for their ability to raise the risk of breast cancer:

the HIA-BC

STEP 4 Pilot test the

proposed HIA-BC by

investigating how well-studied chemicals would perform if tested

STEP 5 Compare assays in the HIA-BC with those in

Federal chemical testing initiatives

Step 1. Events Associated with Breast Cancer

Step 2: Identify test methods (schematic)

http://coeh.berkeley.edu/greenchemistry/cbcrpdocs/matrix.pdf

Consists of three parts:

• Prioritization step

• Rapid Screening Methods

• In vivo studies

Step 3. Hazard Identification Approach for Breast Carcinogens (HIA-BC)

Step 3. HIA-BC: Chemical Prioritization

Step 3. HIA-BC: Rapid Screening Methods

Step 3. HIA-BC: In Vivo Studies

Notes on the Hazard Identification approach for Breast Carcinogens (HIA-BC)

Panel recommended endpoints to test, not specific assays

• The field of toxicity testing is rapidly evolving

• Best practices can evolve with emerging tests

High throughput screens are under development

• Potential to test thousands of chemicals at a range of doses

• Potential to address metabolic differences by testing many possible metabolites

Known to cause breast cancer in

women

Some evidence of breast cancer in

women

Animal mammary carcinogens

Chemicals with suggestive evidence

Carcinogens with no evidence of breast cancer

Alcohol DDT Acrylamide Atrazine Arsenic

Diethylstilbestrol TCDD (dioxin) Benzene Androstenedione Asbestos

Estrogen Ethylene oxide 1,3-Butadiene Dihydrotestosterone Lead (inorganic)

Conjugated estrogens (CE)

Tobacco smoke Dimethylbenz-

anthracene Tamoxifen

HRT (CE + MPA) Medroxyprogesterone

acetate (MPA)

Chemicals not known to cause

cancer

PFOA Caprolactam

Vinyl chloride Benzalkonium

chloride

Step 4: Pilot Testing the HIA-BC

ToxCast – Environmental Protection Agency

Tox21- Interagency (NIEHS, NTP, EPA)

Endocrine Disruptor Screening Program (EDSP)

Step 5: Comparing the HIA-BC Assays To Assays Used In Federal Chemical Screening

Initiatives

Recommendations

1. Chemical testing relevant to breast cancer should include the following endpoints: • Genotoxicity • Cell cycle changes • Endocrine disruption (e.g., estrogenicity) • Altered mammary gland development

Chemical toxicity testing—and the public policies that require it—can inform breast cancer prevention efforts by identifying chemicals that may raise the risk of breast cancer.

2. Design and conduct toxicity tests to consider: • Timing of exposure • Underlying susceptibility factors (e.g., genetic variability, concurrent

exposures)

3. Further research should: • Increase understanding of the biological pathways associated with breast

cancer • Adapt current testing methods to improve their relevance for breast cancer • Develop and validate new toxicity tests, including high throughput screening

methods 4. Apply a similar process to other disease endpoints to develop a comprehensive

approach to identifying chemicals of concern.

More Information

Advocacy materials: • Booklet (spanish translation) • Fact sheet (spanish, chinese, korean) • Freely available online at http://coeh.berkeley.edu/greenchemistry/cbcrp.htm Journal articles: • Overview article on BCCP project and findings (in revision at Environmental

Health Perspectives) • Commentary on need to study mammary gland developmental endpoints

(special issue of Reproductive Toxicology October, 2014)

Full BCCP report available online http://coeh.berkeley.edu/greenchemistry/cbcrp.htm

State of Chemical of Reform

3 bills introduced in the last 2 years - The Safe Chemicals Act of 2013 - Chemical Safety Improvement Act (CSIA) - Chemicals in Commerce Act (CICA)

Growing interest in updating Toxic Substances Control Act 1976 (TSCA)

Tell your Senators to support strong chemical regulation

Encourage your local representatives to support state chemical reform policies

Review emails/website mentioned in the presentation

Science reviews detailed in online databases: silentspring.org/sciencereview

Chemicals & Breast Cancer Advocacy materials http://coeh.berkeley.edu/greenchemistry/cbcrp.htm

Institute of Medicine: A Life Course Approach www.iom.edu/Reports/2011/Breast-Cancer-and-the-Environment-A-Life-Course-Approach.aspx

Reducing Environmental Cancer Risk: What We Can Do Now http://deainfo.nci.nih.gov/advisory/pcp/annualReports/pcp08-09rpt/PCP_Report_08-09_508.pdf

IBCERCC Prioritizing Prevention Report http://www.niehs.nih.gov/about/assets/docs/breast_cancer_and_the_environment_prioritizing_prevention_508.pdf

Join BCAction!

Signup for BCActions’s newsletter and e-alert

www.bcaction.org

Join BCAction on Facebook www.facebook.com/BCAction

Follow BCAction on Twitter twitter.com/BCAction

Spread the word to friends, family, and colleagues

Donate to BCAction www.bcaction.org/donate

Support Our Webinar Series

Your support counts!

If you’ve been inspired today, consider making a donation of $25 or more.

www.bcaction.org/donate

More questions? Contact us! Email: info@bcaction.org Toll-free: 877-2STOPBC

Breast Cancer Action

Challenging Assumptions. Inspiring Change.

www.bcaction.org www.thinkbeforeyoupink.org